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Objective-Recently, mice made deficient in growth arrest-specific gene 6 product (Gas6) or in which Gas6 gene expression was inhibited were shown to have platelet dysfunction and to be less susceptible to thrombosis. The aim of this study was to define and characterize the relevant Gas6 receptor or receptors involved in platelet function. Methods and Results-Using RT-PCR and Western blot analysis we found that mer was the predominantly expressed subtype in mouse and human platelets, whereas axl and rse were not detected. We generated mer-deficient mice by targeted disruption of the mer receptor gene. Platelets derived from mer-deficient mice had decreased platelet aggregation in responses to low concentrations of collagen, U46619, and PAR4 thrombin receptor agonist peptide in vitro. However, the response to ADP was not different from wild-type platelets. Knockout of the mer gene protected mice from collagen/epinephrine-induced pulmonary thromoembolism and inhibited ferric chloride-induced thrombosis in vivo. Tail bleeding times, coagulation parameters, and peripheral blood cell counts in mer-deficient mice were similar to wild-type mice. Key Words: receptor tyrosine kinase Ⅲ Gas6 Ⅲ mer Ⅲ platelet Ⅲ thrombosis M er (c-mer, Nyk, Eyk) 1,2 tyrosine kinase belongs to a family of transmembrane receptors that also includes axl (Ark, Ufo, Tyro7) 3 and rse (Tyro3, Dtk, Etk, Brt, Tif). 4,5 This family of proteins has been implicated in reversible cell growth arrest, 6 survival, 7 proliferation, 7-9 and cell adhesion. 10 -12 Recently, the product of the growth arrest-specific gene 6 (Gas6) was identified as a heterophilic ligand for axl, rse, and mer, whereas protein S was identified as the ligand for the rse receptor. [13][14][15][16] Both Gas6 and protein S belong to the vitamin K-dependent protein family. Proteins in this family, which also includes prothrombin; coagulation factors VII, IX, and X; protein C; and protein Z, are characterized by posttranslational ␥-carboxylation of certain glutamic acid residues by carboxylase, using vitamin K as a cofactor. 6,17 Gas6 is structurally similar to protein S with 48% amino acid identity. Protein S is a cofactor for activated protein C that inactivates the coagulation factors Va and VIIIa 18 and is thus involved in the anticoagulation cascade. Genetic deficiency of protein S in humans is one of the most severe inherited risk factors for thrombosis. 19 Gas6, originally isolated as a growth arrest-specific gene from quiescent fibroblasts, 6 has recently been shown to participate in the regulation of platelet activation and aggregation. 20 Gas6 amplified platelet aggregation and secretion in response to known platelet agonists including ADP, collagen, and the thromboxane A2 analogue U46619. 20 Inactivation of the Gas6 gene prevented venous and arterial thrombosis in mice, and protected against fatal collagen/epinephrine-induced thromboembolism. 20 In addition, Gas6 antibodies inhibited platelet aggregation in vitro and protected mice against fatal thromboembolism in vivo. 20 Con...

Background: Seasonal influenza vaccination coverage remains low in most areas of China. Its influencing factors and barriers in various populations receiving influenza vaccinations need to be well understood to promote vaccination. Methods: A cross-sectional survey was conducted with residents in 48 communities. Vaccination status in the 2018–2019 influenza season and reasons for or against vaccination were surveyed. The potential factors influencing vaccination uptake were determined using bivariate logistic regression. Results: In total, 1301 of the 11053 respondents received an influenza vaccine during the 2018–2019 season with a coverage rate of 11.8% (95% CI, 11.2–12.4). The vaccine coverage was highest among children (26.6%, 95%CI: 24.8–28.5), followed by adults (8.2%, 95%CI: 7.4–9.0) and elderly people (7.3%, 95%CI: 6.5–8.1) ( p < .001). Those with chronic underlying conditions all had higher vaccine coverage than did those without for different groups ( p < .001). Among the three groups, the most common reason for being unvaccinated was worrying about the side effects (45.0%), believing they were healthy and did not need to get vaccinated (42.2%), and lack of influenza vaccine awareness (48.3%). Low education level and lack of awareness were identified as predictors of low coverage rate. Conclusion: Influenza vaccination coverage is low among different populations in Shanghai. Our study highlights the need for appropriate influenza vaccination strategies and programmes targeting different populations.

We have discovered two related chemical series of nonpeptide urotensin-II (U-II) receptor antagonists based on piperazino-phthalimide (5 and 6) and piperazino-isoindolinone (7) scaffolds. These structure types are distinctive from those of U-II receptor antagonist series reported in the literature. Antagonist 7a exhibited single-digit nanomolar potency in rat and human cell-based functional assays, as well as strong binding to the human U-II receptor. In advanced pharmacological testing, 7a blocked the effects of U-II in vitro in a rat aortic ring assay and in vivo in a rat ear-flush model. A discussion of U-II receptor antagonist pharmacophores is presented, and a specifically defined model is suggested from tricycle 13, which has a high degree of conformational constraint.